As yet described above, hearing impairment—herein defined as referring to any hearing defect that can either be congenital or not—is a major concern and a serious burden for Public health.
The early-onset forms of severe deafness are mostly genetic in origin and are frequently due to sensory hair cells defect.
In particular, Usher syndrome (USH) is an autosomal recessive disease that affects both the inner ear and the retina. It is the most frequent cause of hereditary deaf-blindness, affecting 1 child in 25,000.
The following three USH clinical subtypes have been defined:                USH type I (USH1), the most severe, involves severe to profound congenital sensorineural deafness, constant vestibular dysfunction and retinitis pigmentosa with prepubertal onset;        USH2 differing from USH1 mainly in the deafness being less severe, the absence of vestibular dysfunction and the onset of retinitis pigmentosa after puberty; and        USH3 differing from USH1 and USH2 in the progressiveness of hearing loss and the occasional presence of vestibular dysfunction.        
USH1 is genetically heterogeneous. Seven loci responsible for this disease have been defined and called USH1A-G, with four of the corresponding genes having been identified: USH1B, C, D and F. USH1B encodes the actin-based motor protein myosin Vila. USH1C encodes harmonin which is a PDZ domain-containing protein. Mutations in the genes encoding two cadherin-related proteins, cadherin 23 and procadherin 15, have been shown to cause USH1D and USH1F, respectively.
Studies of USH1G-affected families allowed to identify SANS, the human orthologue of the gene defective in Jackson shaker (js) mutant mice, as the causative gene (Mustapha et al., 2002; Weil et al., 2003).
Current clinical approaches to remedy hearing impairment, in particular USH, include hearing aids for mild to moderate impairments and cochlear implants for severe to profound impairments. These existing solutions are however not curative treatments and are not adapted to noisy environments.
There is thus a need in the art for therapeutic approaches to cure genetic forms of human deafness with or without balance defects, in particular USH, yet in particular USH1G.
In this aim, the present inventors studied Ush1g knock-out mice (Ush1g−/− model as described in Caberlotto et al., 2011). This study allowed them to provide a virally-mediated gene therapy for restoring genetically-impaired auditory and vestibular functions. More precisely, their results show that it is possible to efficiently target hair cells and to restore the normal morphology of both cochlear and vestibular hair bundles, which is shown to be critical for auditory and balance functions.
These findings have major therapeutic implications, as described below.